OBJECTIVE: To explore the effect of hypoxia-supported umbilical cord mesenchymal stem cell (UC-MSC) on the expansion of cord blood mononuclear cell （MNC） in vitro. METHODS: The isolated cord blood mononuclear cells were inoculated on the preestablished umbilical cord mesenchymal stem cell layer and cultured under hypoxic conditions (3％ O₂) and the experimental groups were normoxia (MNCs were cultured under normoxic conditions), hypoxia (MNCs were cultured under hypoxic conditions), UC-MSC (MNCs were cultured with UC-MSC under normoxic conditions), and UC-MSC+hypoxia (MNCs were cultured with UC-MSC under hypoxic conditions). To further investigate the combinational effect of 3 factors of SCF+FL+TPO (SFT) on expansion of cord blood MNCs in vitro in hypoxia-supported UC-MSC culture system, the experiments were further divided into group A (MNCs were cultured with UC-MSC and SFT under normoxic conditions), group B (MNCs were cultured with UC-MSC under hypoxic conditions), group C (MNCs were cultured with UC-MSC and SFT under hypoxic conditions). The number of nucleated cells (TNC), CD34⁺ cell, CFU and CD34⁺CXCR4⁺, CD34⁺CD49d⁺, CD34⁺CD62L⁺ cells of each groups were detected at 0, 7, 10 and 14 days, respectively. RESULTS: Compared with group hypoxia and UC-MSC, group UC-MSC+hypoxia effectively promoted the expansion of TNC, CD34⁺ cell and CFU, and upregulated the expression level of adhesion molecule and CxCR4 of the cord blood CD34⁺ cell（P<0.05）. After culturing for 14 days, compared with group A and group B, group C effectively promoted the expansion of cord blood MNC at different time points（P<0.05）, and the effect of group A was better than that of group B at 7 and 10 days（P<0.05）. CONCLUSION Hypoxia-supported UC-MSC efficiently promoted the expansion and expression of adhesion molecule and CXCR4 of cord blood CD34⁺ cell, and the effect of expansion could be enhanced when SFT 3 factors were added.
Humans ; Cells, Cultured ; Fetal Blood ; Cell Proliferation ; Umbilical Cord/metabolism* ; Mesenchymal Stem Cells ; Antigens, CD34/metabolism* ; Hypoxia/metabolism*

Preeclampsia and intrauterine growth restriction (IUGR) of the fetus are the two most common pregnancy complications worldwide, affecting 5%-10% of pregnant women. Preeclampsia is associated with significantly increased maternal and fetal morbidity and mortality. Hypoxia-induced uteroplacental dysfunction is now recognized as a key pathological factor in preeclampsia and IUGR. Reduced oxygen supply (hypoxia) disrupts mitochondrial and endoplasmic reticulum (ER) function. Hypoxia has been shown to alter mitochondrial reactive oxygen species (ROS) homeostasis and induce ER stress. Hypoxia during pregnancy is associated with excessive production of ROS in the placenta, leading to oxidative stress. Oxidative stress occurs in a number of human diseases, including high blood pressure during pregnancy. Studies have shown that uterine placental tissue/cells in preeclampsia and IUGR show high levels of oxidative stress, which plays an important role in the pathogenesis of both the complications. This review summarizes the role of hypoxia-induced mitochondrial oxidative stress and ER stress in the pathogenesis of preeclampsia/IUGR and discusses the potential therapeutic strategies targeting oxidative stress to treat both the pregnancy complications.
Pregnancy ; Female ; Humans ; Placenta ; Fetal Growth Retardation/etiology* ; Pre-Eclampsia/pathology* ; Reactive Oxygen Species ; Hypoxia/pathology* ; Pregnancy Complications/pathology* ; Endoplasmic Reticulum Stress

OBJECTIVES: The energy consumption process of cochlea and neural signal transduction along the auditory pathway are highly dependent on blood oxygen supply. At present, it is under debate on whether the obstructive sleep apnea syndrome (OSAS) would affect the auditory function since the patients suffer from low oxygen saturation. Moreover, it is difficult to detect the functional state of auditory in less severe stage of OSAS. Recently, speech-evoked auditory brainstem response (speech-ABR) has been reported to be a new electrophysiological tool in characterizing the auditory dysfunction. The aim of the present study is to evaluate the auditory processes in adult patients with mild and moderate OSAS by speech-ABR. METHODS: An experimental group of 31 patients with mild to moderate OSAS, and a control group without OSAS diagnosed by apnea hypopnea index in polysomnogram were recruited. All participants underwent otologic examinations and tests of pure-tone audiogram, distortion product otoacoustic emissions, click-evoked auditory brainstem response (click-ABR) and speech-ABR, respectively. RESULTS: The results of pure-tone audiogram, distortion product otoacoustic emissions, and click-ABR in OSAS group showed no significant differences compared with the control group (P>0.05). Speech-ABRs for OSAS participants and controls showed similar morphological waveforms and typical peak structures. There were significant group differences for the onset and offset transient peaks (P < 0.05), where OSAS group had longer latencies for peak V (6.69± 0.33 ms vs. 6.39±0.23 ms), peak C (13.48±0.30 ms vs. 13.31±0.23 ms), and peak O (48.27±0.39 ms vs. 47.60± 0.40 ms) compared to the control group. The latency of these peaks showed significant correlations with apnea hypopnea index for peak V (r=0.37, P=0.040), peak C (r=0.36, P=0.045), as well as peak O (r=0.55, P=0.001). CONCLUSION: These findings indicate that some auditory dysfunctions may be present in patients with mild and moderate OSAS, and the damages were aggravated with the severity of OSAS, which suggests that speech-ABR may be a potential biomarker in the diagnosis and evaluation at early stage of OSAS.
Adult ; Anoxia ; Apnea ; Auditory Pathways ; Cochlea ; Diagnosis ; Evoked Potentials, Auditory, Brain Stem ; Humans ; Oxygen ; Polysomnography ; Signal Transduction ; Sleep Apnea, Obstructive

PURPOSE: In intrahepatic cholangiocarcinoma (iCCA), genetic characteristics on ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG)-PET scans are not yet clarified. If specific genetic characteristics were found to be related to FDG uptake in iCCA, we can predict molecular features based on the FDG uptake patterns and to distinguish different types of treatments. In this purpose, we analyzed RNA sequencing in iCCA patients to evaluate gene expression signatures associated with FDG uptake patterns. METHODS: We performed RNA sequencing of 22 cases iCCA who underwent preoperative ¹⁸F-FDG-PET, and analyzed the clinical and molecular features according to the maximum standard uptake value (SUVmax). Genes and biological pathway which are associated with SUVmax were analyzed. RESULTS: Patients with SUVmax higher than 9.0 (n = 9) had poorer disease-free survival than those with lower SUVmax (n = 13, P = 0.035). Genes related to glycolysis and gluconeogenesis, phosphorylation and cell cycle were significantly correlated with SUVmax (r ≥ 0.5). RRM2, which is related to the toxicity of Gemcitabine was positively correlated with SUVmax, and SLC27A2 which is associated with Cisplastin response was negatively correlated with SUVmax. According to the pathway analysis, cell cycle, cell division, hypoxia, inflammatory, and metabolism-related pathways were enriched in high SUVmax patients. CONCLUSION: The genomic features of gene expression and pathways can be predicted by FDG uptake features in iCCA. Patients with high FDG uptake have enriched cell cycle, metabolism and hypoxic pathways, which may lead to a more rational targeted treatment approach.
Anoxia ; Cell Cycle ; Cell Division ; Cholangiocarcinoma ; Disease-Free Survival ; Fluorodeoxyglucose F18 ; Gene Expression ; Gluconeogenesis ; Glycolysis ; Humans ; Metabolism ; Phosphorylation ; Positron-Emission Tomography ; Sequence Analysis, RNA ; Transcriptome

BACKGROUND: The cerebral blood flow velocity (CBFV) has been known to increase in response to acute hypoxia. However, how CBFV might respond to exercise in hypoxic conditions and be associated with electroencephalogram (EEG) remains unclear. The purpose of this study was to evaluate the effect of exercise in hypoxic conditions corresponding to altitudes of 4,000 m on CBFV and EEG. METHODS: In a randomized, double-blind, balanced crossover study, ten healthy volunteers (19.8±0.4 years) were asked to perform the incremental bicycle ergometer exercise twice in hypoxic and control (sea level) conditions with a 1-week interval, respectively. Exercise intensity was set initially at 50 W and increased by 25 W every 2 minutes to 125 W. Acute normobaric hypoxic condition was maintained for 45 minutes using low oxygen gas mixture. CBFV in the middle cerebral artery (MCA) and EEG were measured at rest 5 minutes, rest 15 minutes, immediately after exercise, and 15 minutes recovery using transcranial-Doppler sonography and EEG signal was recorded from 6 scalp sites leading to analysis of alpha and beta wave relative activities. All data were analyzed using two-way repeated-measures analysis of variance and Pearson's correlation. RESULTS: CBFV in the MCA in the hypoxic condition was significantly higher than that in the control condition at rest 5 minutes (83±9 vs. 69±9 cm/s, P<0.01), rest 15 minutes (87±8 vs. 67±7 cm/s, P<0.001), immediately after exercise (112±9 vs. 97±9 cm/s, P<0.01), and 15 minutes recovery (91±11 vs. 74±7 cm/s, P<0.01). However, no significant correlation was found between the changes of CBFV and EEG wave activities. CONCLUSIONS: These results suggest that the drastic change of CBFV observed during exercise with hypoxia might appear independently with EEG wave activities.
Altitude ; Anoxia ; Cerebrovascular Circulation ; Cross-Over Studies ; Electroencephalography ; Healthy Volunteers ; Middle Cerebral Artery ; Oxygen ; Scalp

PURPOSE: Various publications on the use of sedation and anesthesia for diagnostic procedures in children have demonstrated that no ideal agent is available. Although propofol has been widely used for sedation during esophagogastroduodenoscopy in children, adverse events including hypoxia and hypotension, are concerns in propofol-based sedation. Propofol is used in combination with other sedatives in order to reduce potential complications. We aimed to analyze whether the administration of midazolam would improve the safety and efficacy of propofol-based sedation in diagnostic esophagogastroduodenoscopies in children. METHODS: We retrospectively reviewed the hospital records of children who underwent diagnostic esophagogastroduodenoscopies during a 30-month period. Demographic characteristics, vital signs, medication dosages, induction times, sedation times, recovery times, and any complications observed, were examined. RESULTS: Baseline characteristics did not differ between the midazolam-propofol and propofol alone groups. No differences were observed between the two groups in terms of induction times, sedation times, recovery times, or the proportion of satisfactory endoscopist responses. No major procedural complications, such as cardiac arrest, apnea, or laryngospasm, occurred in any case. However, minor complications developed in 22 patients (10.7%), 17 (16.2%) in the midazolam-propofol group and five (5.0%) in the propofol alone group (p=0.010). CONCLUSION: The sedation protocol with propofol was safe and efficient. The administration of midazolam provided no additional benefit in propofol-based sedation.
Anesthesia ; Anoxia ; Apnea ; Child ; Conscious Sedation ; Endoscopy ; Endoscopy, Digestive System ; Endoscopy, Gastrointestinal ; Heart Arrest ; Hospital Records ; Humans ; Hypnotics and Sedatives ; Hypotension ; Laryngismus ; Midazolam ; Propofol ; Retrospective Studies ; Vital Signs

BACKGROUND: This study was conducted to investigate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on the mobilization of mesenchymal stem cells (MSCs) from the bone marrow (BM) into the peripheral blood (PB) in rats. METHODS: GM-CSF was administered subcutaneously to rats at 50 µg/kg body weight for 5 consecutive days. The BM and PB of rats were collected at 1, 3, and 5 days during the administration for analysis. RESULTS: Upon GM-CSF administration, the number of mononuclear cells increased rapidly at day 1 both in the BM and PB. This number decreased gradually over time in the BM to below the initial amount by day 5, but was maintained at a high level in the PB until day 5. The colony-forming unit-fibroblasts were increased in the PB by 10.3-fold at day 5 of GM-CSF administration, but decreased in the BM. Compared to GM-CSF, granulocyte-colony stimulating factor (G-CSF) stimulated lower levels of MSC mobilization from the BM to the PB. Immunohistochemical analysis revealed that GM-CSF induced a hypoxic and proteolytic microenvironment and increased C-X-C chemokine receptor type 4 (CXCR4) expression in the BM. GM-CSF added to BM MSCs in vitro dose-dependently increased CXCR4 expression and cell migration. G-CSF and stromal cell derived factor-1 (SDF-1) showed similar results in these in vitro assays. Know-down of CXCR4 expression with siRNA significantly abolished GM-CSF- and G-CSF-induced MSC migration in vitro, indicating the involvement of the SDF-1-CXCR4 interaction in the mechanism. CONCLUSION: These results suggest that GM-CSF is a useful tool for mobilizing BM MSCs into the PB.
Animals ; Anoxia ; Body Weight ; Bone Marrow ; Cell Movement ; Granulocyte Colony-Stimulating Factor ; Granulocyte-Macrophage Colony-Stimulating Factor ; In Vitro Techniques ; Mesenchymal Stromal Cells ; Rats ; RNA, Small Interfering ; Stromal Cells

BACKGROUND: Congenital central hypoventilation syndrome (CCHS) is a rare disorder characterized by alveolar hypoventilation and autonomic dysregulation. Patients with CCHS have adequate ventilation while awake but exhibit hypoventilation while asleep. More severely affected patients exhibit hypoventilation both when awake and when asleep. CASE: Here, we report a case of successful spinal anesthesia and postoperative epidural analgesia in a patient with CCHS who underwent orthostatic surgery. CONCLUSIONS: In patients with CCHS, anesthesia is used with the goal of minimizing respiratory depression to avoid prolonged mechanical ventilation. Regional anesthesia should be considered where appropriate. Continuous oxygen saturation and end-tidal carbon dioxide monitoring must be available.
Analgesia, Epidural ; Anesthesia ; Anesthesia, Conduction ; Anesthesia, Spinal ; Anoxia ; Carbon Dioxide ; Humans ; Hypoventilation ; Oxygen ; Respiration, Artificial ; Respiratory Insufficiency ; Ventilation

Whole body ultrasound can be used to improve the speed and accuracy of evaluation of an increasing number of organ systems in the critically ill. Cardiac and abdominal ultrasound can be used to identify the mechanisms and etiology of hemodynamic instability. In hypoxemia or hypercarbia, lung ultrasound can rapidly identify the etiology of the condition with an accuracy that is equivalent to that of computed tomography. For encephalopathy, ocular ultrasound and transcranial Doppler can identify elevated intracranial pressure and midline shift. Renal and bladder ultrasound can identify the mechanisms and etiology of renal failure. Ultrasound can also improve the accuracy and safety of percutaneous procedures and should be currently used routinely for central vein catheterization and percutaneous tracheostomy.
Anoxia ; Brain Diseases ; Catheterization ; Catheters ; Critical Care ; Critical Illness ; Hemodynamics ; Intensive Care Units ; Intracranial Hypertension ; Lung ; Operating Rooms ; Renal Insufficiency ; Tracheostomy ; Ultrasonography ; Urinary Bladder ; Veins

BACKGROUND/AIMS: Many systems including the cardiovascular system (ischemic heart diseases, heart failure, and hypertension) may act as comorbidities that can be seen during the course of chronic obstructive pulmonary disease (COPD). Comorbidities affect the severity and prognosis of COPD negatively. Nearly 25% of patients with COPD die due to cardiovascular diseases. In this study, we aimed to evaluate the relationship between the blood pressure, inflammation, hypoxia, hypercapnia, and the severity of airway obstruction. METHODS: We included 75 COPD patients in the study with 45 control cases. We evaluated age, sex, body mass index, smoking history, C-reactive protein levels, 24-hour ambulatory blood pressure Holter monitoring, arterial blood gas, and respiratory function tests of the patient and the control groups. RESULTS: In COPD patients, the night time systolic, diastolic blood pressures and pulse per minute and the mean blood pressures readings were significantly elevated compared to the control group (p < 0.05). In the correlation analysis, night time systolic pressure was associated with all the parameters except forced expiratory volume in 1 second (FEV₁%). Diastolic blood pressure was associated with pH and HCO₃ levels. The mean night time, day time pulse pressures and 24-hour pulse per minute values were also associated with all the parameters except FEV₁%. CONCLUSIONS: In this study we found that parameters of systolic and diastolic blood pressures and pulse pressures were significantly elevated in COPD patients compared to the control groups. Blood pressure was associated blood gas parameters and inflammation parameters in COPD patients. This, in turn, may cause understanding of the pathophysiology of COPD and its complications.
Airway Obstruction ; Anoxia ; Blood Pressure* ; Body Mass Index ; C-Reactive Protein ; Cardiovascular Diseases ; Cardiovascular System ; Comorbidity ; Electrocardiography, Ambulatory ; Forced Expiratory Volume ; Heart Diseases ; Heart Failure ; Humans ; Hydrogen-Ion Concentration ; Hypercapnia ; Inflammation* ; Prognosis ; Pulmonary Disease, Chronic Obstructive* ; Reading ; Respiratory Function Tests ; Smoke ; Smoking ; Spirometry*